Ginseng is an herb widely used by humans to treat lack of stamina, loss of appetite and cachexia, and impotence. In Asian medicine, ginseng is a common component in herbals used for cancer treatment. There is recent scientific evidence that ginseng and its ginsenoside components are effective in inhibiting cancer cell proliferation in vitro and tumor growth in vivo. Several ginsenosides have been identified that exert anti-cancer activity, yet over 20 ginsenosides exist within ginseng and its extracts. As ginsenosides appear to exert much of the biological activity of ginseng and its extracts, it is important to understand how ginsenosides may interact with each other to influence the anti-cancer potency of ginseng. In preliminary studies, we have found that ginsenosides may augment or antagonize the effects of the anti-cancer ginsenosides. Thus, it is our hypothesis that certain ginsenosides will inhibit human breast cancer cell proliferation via specific mechanisms of action and that other ginsenosides will antagonize or augment the activities of the anti-cancer ginsenosides based on changes in cell proliferation, tumor growth, and gene and protein expression in breast cancer cells. This R21 proposal will address the following aims: To determine the effects of biologically relevant ginsenosides, alone or in combination, on human breast cancer cell proliferation in vitro, we will examine the effects of a wide dose-range of biologically relevant ginsenosides on cell proliferation, identify those ginsenosides with anti-cancer activity, and combine ginsenosides to determine if ginsenoside interactions exist. Secondly, we will determine the mechanisms of action of specific ginsenosides, alone and in combination, on MCF-7 cells. In effect, we will determine the effects of individual ginsenosides on protein expression using a commercial antibody microarray and determine if ginsenoside combinations alter protein expression compared to effects of the individual ginsenosides. Lastly, we will determine the effects of specific ginsenoside combinations on MCF-7 tumor growth in nude mice in vivo. Mice will be inoculated with MCF-7 cells, treated with specific ginsenoside combinations, and tumor growth will be monitored. Identifying the anti-cancer ginsenosides and determining how the other ginsenosides influence their activity, will be an important first step in establishing a ginsenoside profile that will reflect the anti-cancer potency of ginseng products. [unreadable] [unreadable] [unreadable]